Cisplatin Therapy in 41 Dogs With Malignant ... - Wiley Online Library

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Patty L. Bonney, BS, RVT, and Kevin Hahn, DVM. Forty-one dogs .... NA. Died. I day post treatment of sq. cell CA rn -I ? Primary tumor surg. removed; met. lesionĀ ...
Cisplatin Therapy in 41 Dogs With Malignant Tumors Deborah W. Knapp, DVM, Ralph C. Richardson, DVM, Patty L. Bonney, BS, RVT, and Kevin Hahn, DVM

Forty-one dogs with a variety of histopathologically diagnosed, measurable tumors were treated with cisplatin (cis-diamminedichloroplatinum, Platinol, Bristol Laboratories, Syracuse, NY 13221-4755) as a single agent a t a dosage of 60 mg/mZ given intravenously a t 3-week intervals. In an attempt to avoid renal toxicity of cisplatin, saline diuresis was induced and maintained for 4 hours before and 2 hours following cisplatin administration. The dogs received one to ten doses of cisplatin. To determine response to therapy and to monitor toxicity of the drug, the dogs were evaluated with physical examinations including tumor measurements, radiography, complete blood counts, platelet counts, urinalyses, serum urea nitrogen concentrations, and serum creatinine concentrations. An overall response rate of 19% was observed. Complete remission occurred in one of 11 dogs with squamous cell carcinomas and one of one dog with a mediastinal undifferentiated carcinoma. Partial remissions were documented in one of I 1 dogs with squamous cell carcinomas, two of three dogs with metastatic osteosarcomas, one of three dogs with nasal adenocarcinomas, and one of one dog with a thyroid adenocarcinoma. Toxic side effects were primarily gastrointestinal in nature, with vomiting occurring 1-6 hours after cisplatin administration in 27 of 41 dogs. Severe anorexia occurred in three dogs, and hemorrhagic diarrhea was observed in one dog. One dog developed grand ma1 seizures and died 3 hours following therapy. Granulocytopenia was documented in six dogs, and thrombocytopenia was observed in four dogs. One dog showed an increase in serum urea nitrogen and creatinine concentrations, but this patient had known pre-existhg renal disease. These observations of response to therapy and toxicity warrant additional clinical trials to further define cisplatin's role in the treatment of canine neoplasia. (Journal of Veterinary Internal Medicine 1988; 2:41-46)

cisplatin's efficacy against squamous cell carcinoma^,^.^ transitional cell carcinomas,8 an ovarian carcinoma,8 and a pleural adenocarcinoma8 in dogs. Toxicities previously documented in dogs have been limited to gastrointestinal toxicity, bone marrow suppression, and renal to ~ ic ity .~ -Forty-one " dogs with a variety of histopathologically diagnosed, measurable tumors were treated with cisplatin by the Purdue Comparative Oncology Program's Clinical Oncology Section. The dogs were evaluated for response to therapy and toxicity of the drug.

CISPLATIN (cis-diamminedichloroplatinum) is a widely used chemotherapeutic agent in man and is most commonly used against testicular, ovarian, transitional cell, and head and neck carcinomas.'-6 Toxicity of the drug in man frequently includes gastrointestinal toxicity, nephrotoxicity, and bone marrow suppression. Less common toxicities include hypomagnesemia, hypocalcemia, cardiac toxicities, hyperuricemia, peripheial neuropathies, seizures, and anaphylactic reactions.'-6 Cisplatin's application to veterinary medicine has recently been described, and the drug is becoming more popular in the treatment of a variety of solid tumors in dogs.'-'' Previous reports have demonstrated

Materials and Methods Forty-one client-owned dogs with 42 histopathologically diagnosed, measurable tumors were treated with cisplatin as a single agent. Although other modalities of treatment were considered, the final choice of therapy was made by the owner based on expense, access to outpatient therapy, and in a few cases, response in dogs with a similar tumor. The drug was given at a dosage of 60

From the Purdue Comparative Oncology Program, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907-7403. Supported in part by Bristol Laboratories, Syracuse, NY 132214755. Reprint requests: Deborah W. Knapp, DVM, Purdue Cnmparative Oncology Program, School of Veterinary Medicine, Lynn Hall, Purdue University, West Lafayette, IN 47907-7403.

41

Squamous cell CA (axillary) Squamous cell CA (tongue) Squamous cell CA (hard palate) Squamous cell CA (tongue) Squamous cell CA (nasal) Squamous cell CA (vagina) Squamous cell CA (nasal) Squamous cell CA (nasal) Squamous cell CA (oral) Squamous cell CA (tonsil) Osteosarcoma

Osteosarcoma

Osteosarcoma

Thyroid AC

Thyroid CA Hepatic CA Nasal AC

3

13

14

15

16

17

18

12

11

10

9

8

7

6

5

4

2

Undifferentiated CA (mediastinum) Squamous cell CA (digit)

Tumor Type

1

Dog No.

8

NA NA 63

PD PD PR

2

T2,NoM I TzNoM I T3NoMo

21

PR

1

63

NA

PR

SD

T 2J oM I

6

4

63

NA

PD PR

NA

NA

PD

I 2

NA

NA

PD

1

NA NA 330

19

s10+

73

40

150

210

3

NA

127

35

21

36

I20

120

72

1

I35

18

126

720

300+

Survival Time (days)

7

NA

NA

NA

NA

NA

NA

NA

NA

42

570

2 10+

Duration Max. Resp. (days)

PD

1

NA

NA

PD

2 PD

NA

NA

1

5

NA

PD

2

42 NA

PR

5

I50

PD

CR

10

84

Time to Max. Resp. (days)

1

CR

Max. Resp.

5

2

~

No. Doses

TxM I

TxM I

TNM Class.

TABLEI . Results of 41 Dogs Treated with Cisplatin

None

Vomiting, granulocytopenia (granulocytes = 1,674/ mm3), thrombocytopenia (platelts = 32,000/mm3) Vomiting, granulocytopenia (granulocytes = 1,908/ mm') Azotemia (BUN = 60 mg/ dl, creat = 2 mg/dl) None

Vomiting

Vomiting

Vomiting

Vomiting

Vomiting

Vomiting

None

Vomiting

Vomiting

Anorexia

Vomiting

Thrombocytopenia(plate1ets37,000/mm3) Vomiting

Toxicity

PD occurred at 393 days; still alive on different therapy

Azotemic before cisplatin therapy; died of cardiac failure Two primary tumors

Primary tumor surg. removed; PD occured at SO days

Primary tumor surg. removed; met. lesion removed 7 days after PR documented died of pneumonia; no evidence of osteosarcoma Primary tumor surg. removed; met. lesions removed 3 days after PR documented

Died I day post treatment of sq. cell CA

Died of malignant lymphoma; no evidence of sq. cell CA; first 6 cisplatin doses were